In vitro metabolism of 12-methylbenz(a)anthracene: Effect of the methyl group on the stereochemistry of a 5,6-dihydrodiol metabolite

While metabolism of benza]anthracene by rat liver microsomes produced a (+)5R,6R-dihydrodiol as the major enantiomer, metabolism of 12-methylbenza]anthracene under similar conditions gave a (?)5S,6S-dihydrodiol as the major enantiomer. This is the first example indicating that the methyl substituent of a polycyclic aromatic hydrocarbon can drastically alter the stereoselective preference of the microsomal drug-metabolizing enzyme systems toward a substrate molecule in the formation of a dihydrodiol metabolite at an unsubstituted aromatic double bond.